Molecular-epidemiological analysis of Mycobacterium tuberculosis strains isolated in the West-Bohemian Region of the Czech Republic including detailed characterisation of anti-tuberculosis drugs - resistant strains MUDr. Jana Amlerová Abstract Tuberculosis is contagious infectious disease that embodies significant epidemiological and clinical problem worldwide. Tuberculosis incidence differs considerably in various regions of the world but even the countries with low incidence engage strongly in epidemiology of tuberculosis. Tuberculosis belongs to one of the priorities of WHO, cooperation in this matter takes place on a global scale. Tuberculosis is a social illness; accordingly, the countries with high occurrence of tuberculosis are classified as developing countries. Mainly in Africa, there is the situation being complicated by coexistence of HIV. Generally, Europe represents a region with low incidence of tuberculosis. The Czech Republic is a country with the lowest incidence in the world with less than five new cases per 100 000 inhabitants every year. This situation is among others result of high-level tuberculosis surveillance and effective application of epidemiological arrangements based in legislation. This dissertation thesis examines several fields of tuberculosis, mainly focused on modern...

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Orientador: João Pessoa Araujo Junior / Resumo: A segurança dos alimentos é essencial para o desenvolvimento da sociedade e as doenças transmitidas por alimentos (DTAs) acometem milhares de pessoas todos os anos. Dentre os agentes de DTA, Salmonella se destaca como a principal causa de hospitalizações e mortes. A carne suína é uma importante fonte de nutrientes, sendo a mais consumida no mundo. Vários relatos apontaram o isolamento de Salmonella multidrogas resistentes (MDR) associados com a cadeia produtiva dos suínos, e a ocorrência de elementos que possibilitam a transferência de genes de resistência entre populações bacterianas estão diretamente relacionados a essa característica. O presente trabalho objetivou determinar os genes associados com resistência a antimicrobianos de 9 isolados de Salmonella MDR provenientes de linfonodos mesentéricos de suínos, além de aplicar um protocolo in silico para predizer a localização de cada gene (plasmidial ou cromossomal) e detectar e caracterizar a presença de Integrons de resistência. Diversos genes de resistência para a mesma classe de antimicrobianos foram encontrados em cada cepa, e a localização presumida dos genes foi heterogênica, com exceção para os genes de resistência a sulfonamidas, todos classificados como plasmidiais. Cinco cepas apresentaram integrons classe 1, agrupados em três diferentes perfis. A comparação destes perfis com sequências do GenBank revelou que bactérias de diversas espécies, isoladas em diversos países e proveniente de diferentes fontes, inclusive... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Food safety is essential for society development, and foodborne diseases affect thousands of people every year. Among the main foodborne disease agents, Salmonella stands out as the most associated with hospitalizations and deaths. Pork products are an important source of nutrients for population and the most consumed meat in the world. Several reports reveal the presence of Multidrug Resistant (MDR) Salmonella strains in the pork production chain, and the occurrence of elements that allows transference of resistance genes between bacterial populations is related to this characteristic. The present study aimed to determinate the genetic bases associated with Antimicrobial Resistance (AMR) in nine MDR Salmonella strains isolated from swine mesenteric lymph-nodes, beside applying an in-silico protocol to determinate location of the AMR genes (chromosomal or plasmidial) and characterize resistance integrons. Different resistance genes for the same antimicrobial class were present in each strain, and gene localization was heterogenous, except for sulphonamides resistance genes, where all were classified as plasmidial. Five isolates harbored Class 1 ix integrons, which were classified in three distinct Integron Profiles (IPs). Comparison of IPs with sequences of GenBank database revealed that different species of bacteria, from different countries and isolation sources, including human clinical isolates had the same integrons. The diversity of resistance mechanisms for the same an... (Complete abstract click electronic access below) / Doutor

Le neuroblastome est le cancer solide extra-cranial le plus fréquent chez l’enfant. Il est caractérisé par une très grande hétérogénéité tant au niveau clinique que moléculaire. Alors que certains patients rentrent spontanément en rémission, on peut se demander quels facteurs permettent la réémergence du cancer chez d’autres malgré traitement. Pour répondre à cette question, il convient d’identifier chez les patients ayant rechuté, les différentes populations clonales coexistant au diagnostic et/ou à la rechute. Cela permet, entre autre, d’étudier les voies différemment altérées entre ces deux temps. Dans cette optique, nous présentons ici QuantumClone, un algorithme de reconstruction clonal à partir de données de séquençage, ainsi que son application à une cohorte de patients souffrant d’un neuroblastome. Sur ces données, l’application de notre méthode a permis d’identifier des différences dans le ratio de variants prédits fonctionnels par rapport à ceux prédits passagers entre les populations ancestrales, enrichies à la rechute ou appauvries à la rechute. / Neuroblastoma is the most frequent solid extra-cranial cancer of childhood. This cancer displays a high heterogeneity both at clinical and molecular levels. Even though in some patients spontaneous remission can be observed, some others relapse despite treatment and surgical resection. It may be wondered which are the factors that distinguish these two cases. In order to answer this question, identification of populations coexisting at diagnosis and/or relapse in the patients which have relapsed is a prerequisite. This would allow, between other things, to study the pathways differently altered in clones that are specific to each time point. With this in mind, we hereby present QuantumClone, a clonal reconstruction algorithm from sequencing data. In addition, we applied this method to a cohort of patients suffering from neuroblastoma. On these data, our method identified differences in the functional mutation rate, i.e. the number of putative functional variants by total number of variants, between the ancestral clones, clones expanding at relapse, and clones shrinking at relapse.

El Capítulo I trata la actual crisis energética y hace una breve introducción sobre el uso del hidrógeno como vector energético, mencionando los diferentes métodos que pueden utilizarse para la producción/purificación de hidrógeno a partir de recursos renovables. También incluye una breve descripción del papel que puede jugar la biomasa como alternativa a los combustibles fósiles, y su conversión a biocombustibles y productos químicos de valor añadido. El reformado catalítico de glicerol para la producción de gas de síntesis o corrientes ricas en hidrógeno se presenta como una ruta potencial, alternativa y prometedora que ha llamado la atención en los últimos años. Esta reacción se suele llevar a cabo sobre catalizadores basados en metales soportados en materiales estables. En el Capítulo II se estudia el efecto de la adición de Sn sobre las propiedades y la estabilidad de catalizadores de Pt soportado en carbón en la reacción de reformado glicerol en fase gas. Para ello, se preparó y caracterizó una serie de catalizadores con diferentes relaciones atómicas Pt/Sn. El alto precio de los metales nobles motiva la búsqueda y empleo de metales más baratos y abundantes que también tengan un buen comportamiento catalítico en esta reacción. Por ello, en el Capítulo III se emplearon catalizadores basados en Ni promovidos por óxido de cerio para el reformado de glicerol. Por otro lado, se hace necesario optimizar el uso del CeO2 debido a su limitada disponibilidad y sus extensas aplicaciones. Así, en este trabajo se dispersó CeO2 sobre carbón activado de alta área superficial, obteniendo gran superficie de óxido de cerio expuesta al mismo tiempo que se redujo su consumo. También se estudió el efecto de la presencia de estaño en estos catalizadores. Se obtienen diversas ventajas al realizar el reformado de glicerol en fase líquida. Así, se obtienen corrientes más ricas en H2 con menor cantidad de CO. Esto se debe a las moderadas temperaturas y altas presiones empleadas, que favorecen la reacción de desplazamiento del gas de agua. También se suprime la necesidad de evaporar la disolución acuosa de glicerol, por lo que el requerimiento energético es menor y se evitan reacciones indeseadas de descomposición térmica. De este modo, en el Capítulo IV se hace un estudio comparativo sobre las propiedades catalíticas de tres muestras, Pt/CeO2, Ni/CeO2 y Pt-Ni/CeO2, en la reacción de reformado de glicerol en fase líquida. Además, se empleó espectroscopía de reflectancia total atenuada in situ para obtener información relevante sobre los intermedios de reacción y la evolución de los catalizadores durante la reacción, permitiendo así proponer los caminos de reacción más probables. Para obtener corrientes de hidrógeno suficientemente puro para su uso es las pilas de combustible, la corriente obtenida después del reformado debe ser procesada en varias etapas, entre las que se incluyen la eliminación del CO por medio de la reacción de desplazamiento del gas de agua (water-gas shift, WGS). En el Capítulo V se estudia la serie de catalizadores de Ni promovidos por CeO2 soportados en carbón en la reacción de desplazamiento del gas de agua a bajas temperaturas. Para este estudio se emplearon diferentes corrientes de entrada, tanto ideales (sólo CO y H2O) como reales (CO, CO2, H2 y H2O). Por último, en el Capítulo VI, el catalizador que presentó mejor comportamiento catalítico en el apartado anterior fue estudiado en mayor profundidad, relacionando sus propiedades con la actividad catalítica, sometiéndolo finalmente a ensayos de estabilidad en condiciones más demandantes.

The dissertation explores the electronic structures induced by the adsorption of atoms and molecules on surfaces. It focuses on the physical and chemical properties of dispersed metal atom sites on oxide surfaces and the formation of novel molecular structures at hybrid organic-inorganic interfaces. The study uses density functional theory (DFT) calculations to simulate atomic-scale behaviors and aims to contribute to understanding reaction mechanisms and enhancing catalytic activity. Part one investigates the local environments of single platinum atoms on a cerium oxide surface by analyzing their physical and electronic properties. The next part studies the local environments of single platinum atoms dispersed on a cerium oxide surface. Part two compares the water-gas shift reaction for a platinum atom coordinated with a 10-phenanthroline-5,6-dione ligand on titanium oxide with that on a single platinum atom on a titanium oxide surface. It investigates the effect of vacancies in titanium oxide on the electronic structure of platinum and its reactivity. Part three explores the electronic structure of bistable molecules and their potential as molecular switches. Part four analyzes the patterns in scanning tunneling microscope (STM) images of an organic molecule layer on Au(111) and demonstrates electron confinement despite a weak interaction between the molecular layer and the Au surface.

Detta projekt har utförts på Saab Dynamics. Projektets syfte var att utveckla en applikation, TBFO, för att rapportera information om hur missilen GLSDB ska slå till ett mål. TBFO är ämnat för att användas i närheten av målet och information skickas till planeringssystemet GLSDB MPS. Applikationen byggdes runt 3D-motorn Vricon och är anpassat för lättast möjliga användning med pekskärm. Huvuddelen av arbetet berörde utveckling av gränssnitt för pekskärm och utveckling av systemets applikationsprotokoll. Denna rapport redogör för framtagning av systemet samt de verktyg och metoder som användes. Rapporten fördjupar sig inom utveckling av applikationer anpassade för pekskärm. Slutsatsen som kan dras från resultatet av detta projekt är att idén om systemet som utvecklats är användbart för processen att planera angrepp med GLSDB MPS. / This project has been carried out at Saab Dynamics. The project's purpose was to develop an application, TBFO, for reporting information containing how the missile GLSDB would strike a target. TBFO is intended to be used in the proximity of the target and information is sent to the planning system GLSDB MPS. The application was built around the 3D engine from Vricon and is developed to fit for use of touch devices. The main part of the work concerns the development of user interface for touch input and the system’s application protocol. This report describes the processes of developing the system, including what tools and methods that have been used during development. The report also provides an in-depth look at processes used when developing applications for touch devices. The conclusion from the results of this project is that the idea of the described system is useful for the process of planning an assault with GLSDB MPS.

The rare disease pulmonary arterial hypertension (PAH) results in high blood pressure in the lung caused by narrowing of lung arteries. Genes causative in PAH were discovered through family studies and very often harbour rare variants. However, the genetic cause in heritable (31%) and idiopathic (79%) PAH cases is not yet known but are speculated to be caused by rare variants. Advances in high-throughput sequencing (HTS) technologies made it possible to detect variants in 98% of the human genome. A drop in sequencing costs made it feasible to sequence 10,000 individuals including 1,250 subjects diagnosed with PAH and relatives as part of the NIHR Bioresource - Rare (BR-RD) disease study. This large cohort allows the genome-wide identification of rare variants to discover novel causative genes associated with PAH in a case-control study to advance our understanding of the underlying aetiology. In the first part of my thesis, I establish a phenotype capture system that allows research nurses to record clinical measurements and other patient related information of PAH patients recruited to the NIHR BR-RD study. The implemented extensions provide a programmatic data transfer and an automated data release pipeline for analysis ready data. The second part is dedicated to the discovery of novel disease genes in PAH. I focus on one well characterised PAH disease gene to establish variant filter strategies to enrich for rare disease causing variants. I apply these filter strategies to all known PAH disease genes and describe the phenotypic differences based on clinically relevant values. Genome-wide results from different filter strategies are tested for association with PAH. I describe the findings of the rare variant association tests and provide a detailed interrogation of two novel disease genes. The last part describes the data characteristics of variant information, available non SQL (NoSQL) implementations and evaluates the suitability and scalability of distributed compute frameworks to store and analyse population scale variation data. Based on the evaluation, I implement a variant analysis platform that incrementally merges samples, annotates variants and enables the analysis of 10,000 individuals in minutes. An incremental design for variant merging and annotation has not been described before. Using the framework, I develop a quality score to reduce technical variation and other biases. The result from the rare variant association test is compared with traditional methods.

As traditional sources of energy become depleted, significant research interest has gone into conversion of biomass into renewable fuels. Biomass-derived synthesis gas typically contains concentrations of approximately 30 to 600 ppm H2S in stream. H2S is a catalyst poison which adversely affects downstream processing of hydrogen for gas to liquid plants. The water-gas shift reaction is an integral part of converting CO and steam to H2 and CO2. Currently, all known water-gas shift catalysts deactivate in sulfur concentrations typical of biomass-derived synthesis gas. Novel catalysts are needed to remain active in the presence of sulfur concentrations in order to boost efficiency and mitigate costs. Previous studies have shown molybdenum to be active in concentrations of sulfur greater than 300 ppm. Cobalt has been shown to be active as a spinel in concentrations of sulfur less than 240 ppm. Ceria has received attention as a WGS catalyst due to its oxygen donating properties. These elements were synthesized via Pechini's method into various blends of spinel metal oxide solutions. Initial activity testing at lower steam to gas ratios produced near equilibrium conversions for a Ce-Co spinel which remained active in 500 ppm H2S over a temperature range of 350 °C to 400 °C. The catalysts became poisoned and deactivated in higher concentrations of sulfur. Addition of molybdenum to the Ce-Co base had little effect on sulfur tolerance, but it did lead to a reduction in selectivity for methanation. Surface area increased due to adsorbed H2S, and X-Ray Diffraction confirmed that bulk sulfiding did not occur. Incorporation of Ce and Co into a Fe spinel hindered conversion at lower temperatures and deactivated in higher levels of sulfur.

The purpose of this thesis is implementing World Geodetic System (WGS) for Naval Surface Tactical Maneuvering Simulation System (NSTMSS), a High Level Architecture (HLA) based naval simulation, and also implementing body coordinate system for the ships of NSTMSS and its combination with WGS so that NSTMSS can be more accurate, and new ship dynamics models can be integrated to the NSTMSS environment more easily. To improve the coordinate system of NSTMSS these methods were used / World Geodetic System - 1984 (WGS 84) was chosen as the reference system of new coordinate system of NSTMSS and coordinates were transformed to Universal Transverse Mercator (UTM) Coordinate System. Also, the terrains which NSTMSS uses created in OpenFlight (FLT) format with UTM map projection method. In addition to this, Ship Body Coordinate System was implemented as a Cartesian coordinate system. This thesis has achieved improved coordinate systems for the NSTMSS environment to increase the realism of the simulation.